Sleep is essential for survival and poor sleep quality is a principal contributor to chronic diseases. Typically an individual has four to six sleep cycles per night, each between 60 and 120 minutes in length and comprising of different proportions of rapid eye movement (REM) sleep and non-REM sleep (that is further divided into stages N1, N2 and N3). Each sleep cycle typically begins with non-REM sleep and ends with REM sleep. The first half of the night contains most of the N3 or slow wave sleep (SWS), whereas rapid eye movement (REM) sleep is most prominent in the second half. SWS is considered the deepest and most restorative of sleep stages during which there is a reduction in heart rate, blood pressure, sympathetic nervous activity, and brain glucose metabolism, and increase in vagal tone. Hypothalamo-pituitary-adrenal activity is suppressed during SWS and increased during REM sleep. The sequence of sleep stages (NREM sleep stages 1, 2, 3 or the REM sleep stage) during an (overnight) sleep or (daytime) nap, sometimes interrupted with brief periods of wakefulness, is referred to as sleep architecture.
Poor sleep quality resulting from sleep fragmentation or abnormal sleep architecture alters the proportion of REM, non-REM and SWS obtained per night. When a normal individual is chronically sleep deprived, the onset of REM in the first sleep cycle is faster and the total amount of REM and SWS changes. The amount of lighter stages of NREM sleep (stage N1) is decreased. In contrast to this sleep deprivation in a healthy individual, there are a number of medical conditions that contribute to repetitive arousals during the night. This leads to sleep fragmentation and a different sort of chronic inadequate sleep. The frequency of the arousals and their impact on sleep disruption is dependent both on the sleep stage when the arousal occurs and one's susceptibility to sleep disturbances. Individuals are least likely to have arousals or to awaken from an arousal during SWS and most likely during stage N1 NREM and REM sleep. Frequent arousals can disrupt sleep architecture with patterns of awakening that limit the amount of REM and slow wave sleep. Chronic inadequate sleep also manifests in patients who suffer from an inability to easily fall asleep or maintain sleep throughout the night. The assessment of sleep architecture is useful to physicians trying to determine the appropriate diagnosis. For example, in major depression, patients exhibit increased sleep latency, frequent arousals, difficulty remaining asleep, and decreased in slow wave sleep. The first episode of REM sleep will appear earlier than usual, with an increase in total percentage of REM sleep, longer duration REM sleep periods, and increased eye movement density (referred to as REM sleep disinhibition). Patients with post-traumatic stress syndrome can also exhibit abnormal sleep architecture i.e., an increase the amount of REM sleep per night, similar to depressed patients.
Neurological signals i.e., electroencephalograph (EEG) and/or electrooculargram (EOG) are extremely sensitive to the measurement of sleep stage/sleep architecture and sleep quality but fairly insensitive in the assessment of sleep disordered breathing. The detection of arousals during sleep can be measured by multiple means including cortical (i.e., EEG, sympathetic (e.g., electrocardiograph (ECG), pulse rate or peripheral arterial tone), or behavioral (e.g., changes in respiration, movement or position, etc.) approaches. Cortical arousals measured by EEG is the gold-standard measure of sleep disturbance/fragmentation although the reliability of visual scored events may be less sensitive than beat-to-beat changes in cardiac function. The frequency and duration of the arousal, its temporal association with breathing, and the position of the head when the arousal occurs all provide information useful in differentiating the underlying medical condition. For menopausal related sympathetic arousals, the gradual increase in core body temperature that results in a hot flash precedes the arousal during non-REM sleep while the hot flash follows the awakening during REM sleep. The intensity and timing of the hot flash can impact the ability to return to sleep and contributes to sleep maintenance insomnia.
Respiratory effort related arousals are triggered by a full or partial collapse of the upper airway (i.e., sleep disordered breathing or Obstructive Sleep Apnea (OSA)) as a response to return airway patency. The contribution of OSA to poor sleep quality increases the risk of accidents due to daytime drowsiness and has been associated with hypertension, increased risk of congestive heart failure, coronary artery disease, myocardial infarction, cardiac arrhythmias, asthma, diabetes and stroke.
Abnormal subcortical motor system activation associated with periodic limb movements or restless leg syndrome in adults and children can result in arousal sequences similar to OSA that compromise sleep quality and cause sleep deprivation. Environmental conditions such as noise i.e., snoring bed partner, passing vehicles, etc. or sleeping away from home can contribute to delayed sleep onset, abnormal sleep architecture, and increased susceptibility to arousals.
Conventional focused respiratory- or cardio-based approaches are highly sensitive to breathing-related sleep disordered such as OSA but relatively insensitive to the assessment of sleep architecture or sleep quality. In conventional techniques, respiration is measured by multiple means, including airflow, respiratory effort, and/or ECG-related changes. While the most accurate and direct method of monitoring respiratory effort is by measurement of changes in intrathoracic pressure by use of an esophageal catheter, this procedure is invasive and not well tolerated by the patient. Respiratory effort is most commonly measured with bands placed around the chest and abdomen to assess breathing-related change in compartmental circumference. Pulse transit time (PTT) measures the time it takes for a pulse pressure wave to travel from the aortic valve to the periphery. The electrocardiographic (ECG) r-wave is used as the start-time, and the arrival of the pulse at the finger reflects the blood pressure fluctuations induced by negative pleural pressure swings. Diaphragmatic electromyography (EMG) provides a fourth measurement of inspiratory effort and has been shown to have a good correlation with increases in esophageal pressure. Changes in forehead venous pressure represent a new approach that has been shown to measure changes in respiratory effort.
The measurement of airflow is routinely performed by affixing a pressure transducer to a nasal cannula positioned in the nostrils. When a cannula is used measure nasal pressure, the portion inside the nose act as a resistor, and the pressure drop between the nasal cavity and the atmosphere acts like a crude pneumotachometer. The positioning and displacement of the cannula tips inside the nostrils, the size of the nasal openings, and whether the subject is mouth breathing impact the amplitude and shape of the nasal pressure signal. Amplitude variability is less problematic when visual scoring is employed, however amplitude changes can be problematic with mathematically-based measures of tidal volume changes. An advantage of nasal pressure airflow (vs. thermistor or sound-based flow measures) is that shape of airflow signal can be evaluated to assess flow limitation.
Chronically poor sleep quality and associated reduction in SWS results in decreased insulin sensitivity, reduced glucose tolerance and increased risk of type 2 diabetes. Poor sleep quality resulting from menopausal hot flashes is associated with insomnia, depression, anxiety, mood disorders, and cognitive and memory impairment. Low sleep efficiency, abbreviated total sleep time and shortened REM sleep times contributes to the severity of drug-resist hypertension. Sleep deprivation causes an imbalance between leptin and ghrelin (opposing metabolic counterparts which control hunger and food intake) and leads to increased consumption of high carbohydrate foods, weight gain, and obesity. Poor sleep quality unrelated to sleep disordered breathing has been associated with chronic, low-grade inflammation in otherwise healthy young women which increases the risk of future adverse health outcomes. Increased inflammatory markers were found to be sleep duration dependant in women, but not men. Poor sleep quality has explained elevated levels of Interleukin-6 (IL-6), a pro-inflammatory cytokine associated with sleep apnea, narcolepsy, insomnia, excessive daytime drowsiness and fatigue. Elevated IL-6 was strongly associated with decreased sleep efficiency, increased REM latency, and percentage of waking incidences after sleep onset. Other inflammatory markers, such as C-reactive protein are also associated with similar sleep disturbances associated with sleep apnea, and interactions of sleep disturbances and C-reactive protein are associated with cardiovascular diseases. Elevated inflammation is associated with many diseases, including cancer, cardiovascular disease, hypertension, chronic fatigue syndrome, fibromyalgia, depression, and autoimmune disorders among others. Elevated inflammatory cytokines (and other inflammation markers, such as C-reactive protein) are associated with earlier onset of disability in the elderly, increased risk of cardiovascular disease and hypertension, as well as increased risk of diabetes and metabolic X syndrome. In these disease states, elevated inflammation interacts with sleep disturbances in a bi-directional manner to exacerbate the disease state.
It is not uncommon for patients to be misdiagnosed due to overlapping co-morbid symptomology (e.g., untreated OSA to be misdiagnosed as insomnia). Older women are particularly susceptible to misdiagnosis because of the increased risk of OSA as progesterone levels decline and the assumption that menopausal related symptoms are the source of the depressed state or reported problem with sleep. Conversely, patients may be misdiagnosed with OSA when the sleep fragmentation related to the number of cortical or sympathetic arousals is disproportionately greater than a mild case of obstructive breathing event. The overlapping behavioral symptomology of childhood OSA, limb movements during sleep, and Attention Deficit/Hyperactivity Disorder (ADHD) provide other examples where of the difficulty of a differential diagnoses, particularly for a pediatrician with only general knowledge regarding these disorders. Accurate characterization of the etiology of poor sleep quality requires measurement of signals that reflect respiratory, cardiological, and neurological physiology. Thus, it would be useful to simply and easily acquire all sets of measures and combine this information with medical history information and a database of responses to assign pre-test probabilities and/or assist clinicians in constructing their differential diagnoses.